N-of-1 Trial of Electrical Sensory Stimulation Therapy on the Tibial Innervated Area during Gait in a Case of Post-stroke Sensory Disturbance.

Background: Transcutaneous electrical sensory nerve stimulation (TESS) is used to enhance the recovery of sensorimotor function in post-stroke hemiparesis. However, TESS efficacy for post-stroke gait disturbance remains unknown. We hypothesized that TESS on the area innervated by the tibial nerve, targeting the superficial plantar sensation, combined with gait training would improve gait function in patients with gait disturbance caused by severe superficial sensory disturbance after stroke. Case: A 42-year-old man was referred to the convalescent rehabilitation hospital 4 months after a left pontine hemorrhage. He showed severe superficial sensory disturbance without motor paresis in the right lower leg and planta pedis. Gait training with TESS on the tibial nerve innervated area was performed, targeting plantar sensation according to an N-of-1 study design of a single-case ABCAB that included two 10-min sessions of gait training without TESS (phase A), two gait training sessions with TESS targeting the right plantar sensation (phase B), and one session with TESS targeting the upper leg sensation as control (phase C). The patient showed increased gait distance and stride length, improved superficial sensation on the right planta pedis, and improved balance after phase B, but not after phases A and C. Discussion: Gait training with TESS on the tibial nerve innervated area improved gait ability, superficial plantar sensation on the targeted side, and balance function in a post-stroke patient with sensory disturbance. Gait training with TESS may be effective for gait dysfunction caused by sensory disturbance in patients with central nervous system disorders.

Singing Is a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Case-Control Study of Karaoke-Related Coronavirus Disease 2019 Outbreaks in 2 Cities in Hokkaido, Japan, Linked by Whole Genome Analysis.

Background: Singing in an indoor space may increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a case-control study of karaoke-related coronavirus disease 2019 (COVID-19) outbreaks to reveal the risk factors for SARS-CoV-2 infection among individuals who participate in karaoke. Methods: Cases were defined as people who enjoyed karaoke at a bar and who tested positive for SARS-CoV-2 by reverse-transcription polymerase chain reaction between 16 May and 3 July 2020. Controls were defined as people who enjoyed karaoke at the same bar during the same period as the cases and tested negative. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. ORs of key variables adjusted for each other were also estimated (aOR). Results: We identified 81 cases, the majority of whom were active elderly individuals (median age, 75 years). Six cases died (case fatality ratio, 7%). Among the cases, 68 (84%) were guests, 18 of whom had visited ≧2 karaoke bars. A genome analysis conducted in 30 cases showed 6 types of isolates within 4 single-nucleotide variation difference. The case-control study revealed that singing (aOR, 11.0 [95% CI, 1.2-101.0]), not wearing a mask (aOR, 3.7 [95% CI, 1.2-11.2]), and additional hour spent per visit (aOR, 1.7 [95% CI, 1.1-2.7]) were associated with COVID-19 infection. Conclusions: A karaoke-related COVID-19 outbreak that occurred in 2 different cities was confirmed by the results of genome analysis. Singing in less-ventilated, indoor and crowded environments increases the risk of acquiring SARS-CoV-2 infection. Wearing a mask and staying for only a short time can reduce the risk of infection during karaoke.

The Coevolution of Cellularity and Metabolism Following the Origin of Life.

The emergence of cellular organisms occurred sometime between the origin of life and the evolution of the last universal common ancestor and represents one of the major transitions in evolutionary history. Here we describe a series of artificial life simulations that reveal a close relationship between the evolution of cellularity, the evolution of metabolism, and the richness of the environment. When environments are rich in processing energy, a resource that the digital organisms require to both process their genomes and replicate, populations evolve toward a state of non-cellularity. But when processing energy is not readily available in the environment and organisms must produce their own processing energy from food puzzles, populations always evolve both a proficient metabolism and a high level of cellular impermeability. Even between these two environmental extremes, the population-averaged values of cellular impermeability and metabolic proficiency exhibit a very strong correlation with one another. Further investigations show that non-cellularity is selectively advantageous when environmental processing energy is abundant because it allows organisms to access the available energy, while cellularity is selectively advantageous when environmental processing energy is scarce because it affords organisms the genetic fidelity required to incrementally evolve efficient metabolisms. The selection pressures favoring either non-cellularity or cellularity can be reversed when the environment transitions from one of abundant processing energy to one of scarce processing energy. These results have important implications for when and why cellular organisms evolved following the origin of life.

Study on structure-activity relationship of vitamin K derivatives: Conversion of the naphthoquinone part into another aromatic ring and evaluation of their neuronal differentiation-inducing activity.

We synthesized novel vitamin K derivatives by converting the naphthoquinone group to benzene derivatives and benzoquinone. We evaluated their neuronal differentiation activities to investigate the effect of the quinone moiety on this process. We observed that the 1,4-quinone as well as the side chain part play important roles in neuronal differentiation. We also performed QSAR analysis to predict the compounds which would have higher differentiation activity.

Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities.

Vitamin K is an essential cofactor of γ-glutamylcarboxylase as related to blood coagulation and bone formation. Menaquinone-4, one of the vitamin K homologues, is biosynthesized in the body and has various biological activities such as being a ligand for steroid and xenobiotic receptors, protection of neuronal cells from oxidative stress, and so on. From this background, we focused on the role of menaquinone in the differentiation activity of progenitor cells into neuronal cells and we synthesized novel vitamin K derivatives with modification of the ω-terminal side chain. We report here new vitamin K analogues, which introduced an alkylated phenyl group at the ω-terminal side chain. These compounds exhibited potent differentiation activity as compared to control.

Photoirradiation wavelength dependence of cycloreversion quantum yields of diarylethenes.

The cycloreversion quantum yields of compounds 1b and 2b increased upon irradiation with light at shorter wavelengths. The irradiation wavelength dependence is ascribed to the energy barrier on the 2A potential energy surface in the excited electronic state.

Photoswitchable fluorescent diarylethene derivatives with short alkyl chain substituents.

The sulfone derivatives of 1,2-bis(2-alkyl-6-phenyl-1-benzothiophen-3-yl)perfluorocyclopentene having various short alkyl chain substituents at reactive carbons were prepared and the effect of alkyl substitution on the fluorescence property of the closed-ring isomers was studied. Upon irradiation with ultraviolet (UV) light the derivatives exhibit a brilliant green fluorescence under irradiation with visible (> 400 nm) light, while the fluorescence disappears upon irradiation with visible (> 400 nm) light alone. The fluorescence quantum yield of the methyl substituted derivative (1b) dramatically decreases from 0.84 to 0.15 when the solvent is changed from hexane to acetonitrile, while the changes of ethyl, n-propyl and n-butyl substituted derivatives (2b)­(4b) are moderate. The quantum yields of (2b)­(4b) are kept to values close to 0.7 even in polar acetonitrile. The fluorescence lifetime measurement revealed that efficient non-radiative decay processes took place in (1b) in polar solvent, while their contribution to the deactivation was not so large in (2b)­(4b). The neighboring short alkyl chains at the connecting carbons are considered to defend the sulfone units against the attack of polar solvent molecules and weaken the solvent polarity effect.

Low-intensity pulsed ultrasound activates the phosphatidylinositol 3 kinase/Akt pathway and stimulates the growth of chondrocytes in three-dimensional cultures: a basic science study.

INTRODUCTION: The effect of low-intensity pulsed ultrasound (LIPUS) on cell growth was examined in three-dimensional-cultured chondrocytes with a collagen sponge. To elucidate the mechanisms underlying the mechanical activation of chondrocytes, intracellular signaling pathways through the Ras/mitogen-activated protein kinase (MAPK) and the integrin/phosphatidylinositol 3 kinase (PI3K)/Akt pathways as well as proteins involved in proliferation of chondrocytes were examined in LIPUS-treated chondrocytes. METHODS: Articular cartilage tissue was obtained from the metatarso-phalangeal joints of freshly sacrificed pigs. Isolated chondrocytes mixed with collagen gel and culture medium composites were added to type-I collagen honeycomb sponges. Experimental cells were cultured with daily 20-minute exposures to LIPUS. The chondrocytes proliferated and a collagenous matrix was formed on the surface of the sponge. Cell counting, histological examinations, immunohistochemical analyses and western blotting analysis were performed. RESULTS: The rate of chondrocyte proliferation was slightly but significantly higher in the LIPUS group in comparison with the control group during the 2-week culture period. Western blot analysis showed intense staining of type-IX collagen, cyclin B1 and cyclin D1, phosphorylated focal adhesion kinase, and phosphorylated Akt in the LIPUS group in comparison with the control group. No differences were detected, however, in the MAPK, phosphorylated MAPK and type-II collagen levels. CONCLUSION: LIPUS promoted the proliferation of cultured chondrocytes and the production of type-IX collagen in a three-dimensional culture using a collagen sponge. In addition, the anabolic LIPUS signal transduction to the nucleus via the integrin/phosphatidylinositol 3-OH kinase/Akt pathway rather than the integrin/MAPK pathway was generally associated with cell proliferation.